While rates of adult cigarette smoking continue to decline, smokeless tobacco (ST) use is increasing. Since 2005, virtually every major producer of cigarettes has entered the market for ST. Some are producing products using their popular cigarette brand names (e.g., Marlboro Snus, Camel Snus, Lucky Strike Snus). The proliferation of these new products is adding to the already wide array of available non-smoked tobacco (e.g., moist snuff, chewing tobacco, iqmik, pellets). Characterizing these ST products in such a rapidly changing landscape requires more rapid means than traditional long term cross-over trials. This is a proposal to apply acute testing measures to better understand the consequences of human use of varying ST products. We will perform a series of acute cross-over trials, systematically testing ST products currently on the market, and any introduced in the course of the work to determine their abuse liability and potential toxicity. To that end, we propose the following specific aims: To characterize and contrast the abuse liability potential and likelihood of adoption of a range of ST products. Abuse liability assessment (ALA) of ST will include liking and relief of craving/withdrawal and neurocognitive function (EEG spectral analysis and event- related potentials) in comparison to medicinal nicotine (control with known low abuse potential); to characterize and contrast the potential toxicity of ST products using boost biomarkers that are sensitive to one-time use of a tobacco product, including salivary tobacco-specific nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) and exhaled breath volatile organic compounds (VOCs), all measured before and after single-use of each product; and, to characterize and contrast the potential toxicity and abuse potential of ST products by measuring levels of VOCs emitted from a range of ST products, as well as product levels of TSNAs and PAHs, and assessing pH, moisture, total nicotine, and free nicotine levels. PUBLIC HEALTH RELEVANCE: Every major U.S. manufacturer of cigarettes has entered the smokeless tobacco market. From the November 2002 the National Tobacco Monitoring Research and Evaluation Workshop came recommendations for surveillance of the tobacco vector, including developing systems for monitoring tobacco ingredients and emissions, and uptake of constituents by users. This proposal is in response to that call to action, and will test a rapid through-put method of characterizing the abuse liability and potential toxicity of the plethora of new non-smoked tobacco products entering the market.